title: Epigenetic silencing of CXCL14 induced colorectal cancer migration and invasion.
abstract: To explore epigenetic regulation and the impact of chemokine CXCL14 on colorectal cancer, 7 colorectal cancer cell lines, 107 cases of primary colorectal cancer, and 10 cases of normal colorectal mucosa were evaluated in this study. Methylation specific PCR (MSP), semi-quantitative reverse-transcription PCR (RT-PCR), cell proliferation assay, colony formation, and transwell assay were performed for the evaluation. Complete methylation and loss of CXCL14 expression were found in 5 colorectal cancer cell lines. Partial methylation and weak expression were found in two cell lines. CXCL14 was methylated in 79.4% (85/107) of primary human colorectal cancer. No methylation was found in 10 cases of normal colorectal mucosa. Restoration of CXCL14 expression was induced by the 5-aza-2'-deoxycytidine (DAC) treatment. The cell viability was reduced and colony formation was inhibited by restoration of CXCL14 expression in HCT116 cells, a colorectal cancer cell line. The number of invasive and migration cells was reduced by CXCL14. The expression of MMP-2, Vimentin, and NF-κB was suppressed, and the expression of E-cadherin and IκB-α was induced by CXCL14. In conclusion, CXCL14 is frequently methylated in human colorectal cancer and promoter region hypermethylation silenced CXCL14 expression in colorectal cancer cells. Restoration of CXCL14 expression suppressed colorectal cancer proliferation. CXCL14 inhibits colorectal cancer migration, invasion, and epithelial-to-mesenchymal transition (EMT) by suppressing NF-κB signaling.
authors.affiliation: Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100853, China and College of Medicine, NanKai University, Tianjin 300071, China.
authors.forename: Baoping
authors.initials: B
authors.lastname: Cao
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Yang
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Pan
authors.forename: Yan
authors.initials: Y
authors.lastname: Jia
authors.forename: Malcolm V
authors.initials: MV
authors.lastname: Brock
authors.forename: James G
authors.initials: JG
authors.lastname: Herman
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Guo
mesh_terms: D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D019743:Chemokines, CXC / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D019175:DNA Methylation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic / Q000235:genetics; D014746:Vimentin / Q000378:metabolism
chemical_list: C118056:CXCL14 protein, human; D015820:Cadherins; D019743:Chemokines, CXC; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014746:Vimentin; D000072000:NF-KappaB Inhibitor alpha; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2